Carol J. Soroka, Ph.D.

Associate Research Scientist
Section of Digestive Diseases

Research Interests

The hepatocyte is a highly polarized epithelial cell whose apical canalicular membrane contains specific transporters which are responsible for the excretion of many substances into the biliary space. I am interested in the regulation of trafficking of these membrane proteins to their site of function. Utilizing an in vitro isolated rat hepatocyte couplet model we have shown that membrane transporters such as the bile salt export pump and the multi-drug resistance protein reside in a vesicular compartment under basal conditions. These vesicles can be stimulated to fuse with the apical membrane by DBcAMP treatment. This is accompanied by an increase in secretion of bile acids and organic anions. Depolymerization of microtubules inhibit both the relocalization and the secretion. Immunoelectron microscopy has demonstrated that the transporters colocalize with polymeric IgA receptor on a population of transcytotic vesicle which is approximately 140 nm in diameter. Future work is being conducted to visualize vesicle movement in live cells and to understand second messenger regulation.

Selected Publications

• Lee, J.M., Trauner, M., Soroka, C.J., Stieger, B., Meier, P.J. and Boyer, J.L. (2000) Expression of the Bile Salt Export Pump is Maintained after Chronic Cholestasis in the Rat. Gastroenterology 118: 163-172.
• Soroka, C.J., Pate, M.K. and Boyer, J.L. (1999) Canalicular Export Pumps Traffic with Polymeric Immunoglobulin A Receptor on the Same Microtubule-associated Vesicle in Rat Liver. J. Biol. Chem. 274: 26416-26424.
• Beuers, U., Probst, I., Soroka, C., Boyer, J.L., Kullak-Ublick, G-A. and Paumgartner, G. (1999) Modulation of Protein Kinase C by Taurolithocholic Acid in Isolated Rat Hepatocytes. Hepatology 29: 477-482.
• Hayes, J., Soroka, C.J., Rios-Velez, L. and Boyer, J.L. (1999) Hepatic Sequestration and Modulation of the Canalicular Transport of the Organic Cation, Daunorubicin, in the Rat. Hepatology 29: 483-493.
• Sun, A-Q., Ananthanarayanan, M., Soroka, C.J., Thevananther, S., Shneider, B.L. and Suchy, F.J. (1998) Sorting of Rat Liver and Ileal Sodium-Dependent Bile Acid Transporters in Polarized Epithelial Cells. Am. J. Physiol. 275: G1045-G1055.
• Roelofsen, H., Soroka, C.J., Keppler, D. and Boyer, J.L. (1998) Cyclic AMP Stimulates Sorting of the Canalicular Organic Anion Transporter (Mrp2/cMOAT) to the Apical Domain in Hepatocyte Couplets. J. Cell Sci. 111: 1137-1145.
• Ford, M.G., Del Valle, J., Soroka, C.J. and Merchant, J.L. (1997) EGF Receptor Activation Stimulates Endogenous Gastrin Gene Expression in Canine G Cells and Human Gastric Cell Cultures. J. Clin. Invest. 99: 2762-2771.
• Trauner, M., Arrese, M., Soroka, C.J., Ananthanarayanan, M., Koeppel, T.A., Schlosser, S.F., Such, F.J., Keppler, D. and Boyer, J.L. (1997) The Rat Canalicular Conjugate Export Pump (Mrp2) is Down-regulated in Intrahepatic and Obstructive Cholestasis. Gastroenterology 113: 255-264.
• Matovcik, L.M., Maranto, A.R., Soroka, C.J., Gorelick, F.S., Smith, J. and Goldenring, J.R. (1996) Co-distribution of Calmodulin-dependent Protein Kinase II and Inositol Triphosphate Receptors in an Apical Domain of Gastrointestinal Mucosal Cells. J. Histochem. Cytochem. 44: 1243-1250.
• Gartung, C., Ananthanarayanan, M., Rahman, M.A., Soroka, C.J., Stolz, A., Suchy, F.J. and Boyer, J.L. (1996) Down-regulation of Expression and Function of the Hepatic Sodium-Dependent Bile Acid Cotransporter in Extrahepatic Cholestasis. Gastroenterology 110: 199-209.
• Boyer, J.L and Soroka, C.J. (1995) Vesicle Targeting to the Apical Domain Regulates Bile Excretory Function in Isolated Rat Hepatocyte Couplets. Gastroenterology 109: 1600-1611.

Contact

Campus Address
Department of Internal Medicine
333 Cedar Street (LMP 1080)
New Haven, CT 06520

E-mail
carol.soroka@yale.edu

Office Phone
(203) 785-3151